Substitutes Martin Caceres and Paul Pogba both struck in the last 10 minutes to earn the Bianconeri all three points at the Juventus Stadium.
It was Napoli's first defeat of the season, their second to Juventus when considering the Italian Supercoppa between the two sides in August.
With assistant boss Angelo Alessio on the Juve bench for the first time after his suspension for match-fixing was reduced, it was business as usual for the Turin-based club as they await the return of head coach Antonio Conte in December.
They had to work hard for their win, though, and Napoli went close in the first half when Edinson Cavani curled a free-kick on to the crossbar.
Lazio kept up their excellent form with a 3-2 win over a struggling but defiant AC Milan at the Stadio Olimpico.
Hernanes, Antonio Candreva and Miroslav Klose put Lazio firmly in the driving seat at 3-0 up, but goals from Nigel de Jong on the hour mark and a Stephan El Shaarawy strike 10 minutes later set up a grandstand finish.
However, Lazio held on to all three points, taking them up to third in the table and leaving Milan just two points above the relegation zone in 13th after a fifth defeat in eight league matches.
Saturday's Serie A Results
Sunday's Serie A Fixtures